PO.CTP01.03 · 进行中的临床试验
DiscovHER PAN-206：一项在既往接受过治疗的人表皮生长因子受体2过表达实体瘤患者中开展的zanidatamab 2期泛肿瘤研究
DiscovHER PAN-206: Phase 2 tumor-agnostic study of zanidatamab in patients with previously treated human epidermal growth factor receptor 2-overexpressing solid tumors
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摘要 Abstract
中文摘要
背景：组织不可知的HER2靶向治疗是治疗HER2表达肿瘤的一种合理的精准肿瘤学方法，因为该蛋白在多种肿瘤类型中表达并具有潜在的致癌作用。Zanidatamab是一种HER2双靶向双特异性抗体，基于2期HERIZON-BTC-01试验，已获美国食品药品监督管理局批准作为单药治疗既往接受过治疗、不可切除或转移性HER2阳性免疫组化（IHC）3+胆道癌（BTC）成人患者。在62例既往接受过治疗的BTC患者中，经确认的客观缓解率（cORR）为52%，中位缓解持续时间（DOR）为14.9个月。在一项针对既往接受过大量治疗的多种HER2表达实体瘤患者的1期研究中，zanidatamab还展现出令人鼓舞的抗肿瘤活性和可管理的安全性特征。
方法：DiscovHER PAN-206（NCT06695845）是一项开放标签、单臂、多中心研究，评估zanidatamab单药治疗在经中心评估为HER2 IHC 3+、局部晚期、不可切除或转移性实体瘤（BTC除外）、既往接受过≥1种抗癌治疗且无确认获益的可用治疗选择的成人患者中的疗效。符合条件的患者必须有东部肿瘤协作组体能状态0或1，并有经独立中心审查（ICR；按实体瘤缓解评估标准1.1版）确认的可测量病灶。患者将入组3个队列：队列1（除乳腺癌[BC]和胃食管腺癌[GEA]之外的任何实体瘤）、队列2（BC）和队列3（GEA）。队列1不允许既往HER2靶向治疗；队列2和3要求既往接受过曲妥珠单抗德鲁替康（trastuzumab deruxtecan）治疗。Zanidatamab将以每3周一次静脉给药，剂量为1800 mg（体重<70 kg患者）或2400 mg（体重≥70 kg患者），直至疾病进展或不可接受的毒性。主要终点为按ICR评估的cORR。次要终点包括总生存期和不良事件发生频率；研究者评估的cORR；以及按ICR和研究者评估的DOR、至缓解时间、疾病控制率和无进展生存期。探索性终点包括患者报告结局。本试验正在开放招募。最初在2025年欧洲肿瘤内科学会年会上发表。
查看英文原文 English abstract
Background: Tissue-agnostic HER2 targeting is a rational, precision-oncology approach for treating HER2-expressing tumors due to the protein's expression across multiple tumor types and potential oncogenic role. Zanidatamab, a dual HER2-targeted bispecific antibody, is approved as monotherapy by the US Food and Drug Administration for adults with previously treated, unresectable or metastatic HER2-positive immunohistochemistry (IHC) 3+ biliary tract cancer (BTC) based on the phase 2 HERIZON-BTC-01 trial. In 62 patients with previously treated BTC, the confirmed objective response rate (cORR) was 52% and the median duration of response (DOR) was 14.9 months. Zanidatamab has also shown encouraging antitumor activity with a manageable safety profile in a phase 1 study of heavily pretreated patients with various HER2-expressing solid tumors.
Methods: DiscovHER PAN-206 (NCT06695845) is an open-label, single-arm, multicenter study of zanidatamab monotherapy in adults with centrally assessed HER2 IHC 3+, locally advanced, unresectable or metastatic solid tumors (except BTC) who received ≥1 prior anticancer therapy and have no available treatment options with confirmed benefit. Eligible patients must have an Eastern Cooperative Oncology Group performance status of 0 or 1 and measurable disease by independent central review (ICR; per Response Evaluation Criteria in Solid Tumors version 1.1). Patients will be enrolled into 3 cohorts: cohort 1 (any solid tumor except breast cancer [BC] and gastroesophageal adenocarcinoma [GEA]), cohort 2 (BC), and cohort 3 (GEA). No prior HER2-targeted therapy is allowed for cohort 1; prior treatment with trastuzumab deruxtecan is required for cohorts 2 and 3. Zanidatamab will be administered intravenously once every 3 weeks at 1800 mg (patients <70 kg) or 2400 mg (patients ≥70 kg), until disease progression or unacceptable toxicity. The primary endpoint is cORR per ICR. Secondary endpoints include overall survival and frequency of adverse events; cORR per investigator; and DOR, time to response, disease control rate, and progression-free survival per ICR and investigator assessment. Exploratory endpoints include patient-reported outcomes. This trial is open for enrollment. Originally presented at the 2025 European Society for Medical Oncology Annual Meeting.
利益披露 Disclosure
V. Subbiah,
Abbvie ), Other, consulting/advisory role.
Bayer HealthCare Pharmaceuticals, Inc ), Other, consulting/advisory role.
F. Hoffmann-La Roche ), Other, consulting/advisory role.
Illumina Other, consulting/advisory role; other professional activities.
Incyte Corporation ), Travel, Other, consulting/advisory role.
Jazz Pharmaceuticals, Inc. Other, consulting/advisory role; support for other professional activities.
LabCorp Other, consulting/advisory role.
Regeneron Pharmaceuticals, Inc Other, consulting/advisory role.
Relay Therapeutics ), Other, consulting/advisory role.
Aadi Biosciences Other, Support for other professional activities.
Clinical Care Communications Other, Support for other professional activities.
Med Learning Group Other, Support for other professional activities.
Medscape Other, Support for other professional activities.
Phenon Therapeutics Other, Support for other professional activities.
AgenSys, Alfa-Sigma, Altulum, Amgen, Berghealth, Blueprint Medicines, Boston Biomedical, Boston Pharmaceuticals, Celgene Corporation, Dragonfly Therapeutics, Exelixis Inc ).
FUJIFILM Medical Systems USA, Inc; Genentech USA, Inc; GlaxoSmithKline; Idera Pharma; Inhibrx; LOXO Oncology, LLC; MedImmune; Multivir; Nanocarrier; NCCN; NCI; Novartis Pharma; OncLive; Oncusp; PERS ).
Pfizer; PharmaMar; Takeda Oncology ).
ASCO; ESMO Travel.
Helsinn Healthcare SA Travel.
V. Makker,
ArQule; Clovis; Duality; Eisai; Faeth Therapeutics; GlaxoSmithKline; IBM Watson; ITeos Therapeutics; Kartos Therapeutics; Karyopharm; Lilly; Merck; Novartis; and Takeda Other, consulting or advisory role.
AstraZeneca; Bayer; Bristol Myers Squibb; Clovis; Duality; Eisai; Faeth Therapeutics; Karyopharm Therapeutics; Lilly; Merck; Takeda; and Zymeworks ).
Eisai; Karyopharm Therapeutics; and Merck Travel, accommodations and expenses.
IBM Other.
D. Oh,
Arcus Biosciences; ASLAN Pharmaceuticals; AstraZeneca; Bayer; Basilea; BeiGene; Celgene; Genentech/Roche; Halozyme; IQVIA; Merck Serono; MSD Oncology; Novartis; and Taiho Pharmaceutical; Other, consulting or advisory role.
Turning Point Therapeutics; Yuhan; and Zymeworks Other, consulting or advisory role.
Array BioPharma; AstraZeneca; BeiGene; Eli Lilly; Handok; MSD; Novartis; and SERVIER ).
E. Gardener,
Jazz Pharmaceuticals Employment, Stock, Stock Option.
E. Gartner,
Jazz Pharmaceuticals Employment.
Jazz Pharmaceuticals; and Zymeworks Stock, Stock Option.
F. Meric-Bernstam,
MD Anderson Cancer Center Employment.
Apeiron Biologics; AstraZeneca; Biovica; Black Diamond Therapeutics; Calibr; EcoR1 Capital; Eisai; F. Hoffmann-La Roche; Infinity Pharmaceuticals; Karyopharm Therapeutics; LegoChem Biosciences; Other, consulting or advisory role.
Lengo Therapeutics; LOXO-Oncology; Menarini Group; OnCusp Therapeutics; PACT Pharmaceuticals; Seattle Genetics; Tallac Therapeutics; Theratechnologies; and Zymeworks Other, consulting or advisory role.
AbbVie; Aileron Therapeutics; AstraZeneca; Bayer; Boehringer Ingelheim; Calithera Biosciences; CytomX Therapeutics; Curis; Daiichi-Sankyo; Debiopharm Group; eFFECTOR Therapeutics; Genentech; ).
GlaxoSmithKline; Guardant Health; Jounce Therapeutics; Klus Pharma; Novartis; Pfizer; PUMA Biotechnology; Seattle Genetics; Taiho Pharmaceutical; Taiho Pharmaceutical Co; Takeda; and Zymeworks ).
the Cholangiocarcinoma Foundation; the European Organisation for Research and Treatment of Cancer (EORTC); and the European Society for Medical Oncology (ESMO) Travel, accommodations and expenses.